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Details on Person UniProt:O43151 TET3

Class:Id	ReferenceGeneProduct:67592
_chainChangeLog	chain:1-1660 added on Sat February 7 2015;chain:1-1660 for 67592 removed on Sun February 16 2020;chain:1-1795 for 67592 added on Sun February 16 2020
_displayName	UniProt:O43151 TET3
_timestamp	2025-08-15 22:04:53
chain	chain:1-1795
checksum	7D1041E2C45C4F18
comment	FUNCTION Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization (PubMed:31928709). Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation (By similarity). Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes (PubMed:23217707). In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin (By similarity). In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT (PubMed:23353889). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034).CATALYTIC ACTIVITY a 5-methyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-hydroxymethyl-2'-deoxycytidine in DNA + succinate + CO2CATALYTIC ACTIVITY a 5-hydroxymethyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-formyl-2'-deoxycytidine in DNA + succinate + CO2 + H2OCATALYTIC ACTIVITY a 5-formyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-carboxyl-2'-deoxycytidine in DNA + succinate + CO2 + H(+)COFACTOR Binds 1 Fe(2+) ion per subunit.COFACTOR The zinc ions have a structural role.SUBUNIT Interacts with HCFC1 (PubMed:23353889). Interacts with OGT (PubMed:23222540, PubMed:23353889). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (PubMed:24357321, PubMed:25557551).INTERACTION At the zygotic stage, localizes in the male pronucleus, while it localizes to the cytoplasm at other preimplantation stages. Binds to the promoter of target genes, close to the transcription start site.ALTERNATIVE PRODUCTS Expressed in colon, muscle, adrenal gland and peripheral blood lymphocytes.DEVELOPMENTAL STAGE Expressed in fetal brain but not adult brain.DOMAIN The CXXC zinc finger mediates binding to CpG-DNA (PubMed:29276034). It mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence motifs (By similarity).PTM Monoubiquitinated at Lys-994 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the TET family.CAUTION Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.
description	recommendedName: fullName evidence="16"Methylcytosine dioxygenase TET3 ecNumber evidence="12"1.14.11.80
geneName	TET3 CXXC10 KIAA0401
identifier	O43151
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Chromatin regulator Chromosome Cytoplasm Developmental protein Dioxygenase Disease variant DNA-binding Intellectual disability Iron Isopeptide bond Metal-binding Nucleus Oxidoreductase Proteomics identification Reference proteome Ubl conjugation Zinc Zinc-finger
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	TET3
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8993357] ENSEMBL:ENSG00000187605 TET3 [Homo sapiens]
secondaryIdentifier	TET3_HUMAN A6NEI3 J3KNF3 K9JJH7 Q86Z24 Q8TBM9
sequenceLength	1795
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:233409] UniProt:O43151-2 TET3 [Homo sapiens] [ReferenceIsoform:356930] UniProt:O43151-3 TET3 [Homo sapiens] [ReferenceIsoform:401486] UniProt:O43151-1 TET3 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:5220918] TET3 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:O43151 TET3 (67592)